Antipsychotics and Metabolics in the post-CATIE era

Abstract

Schizophrenia patients have high prevalence of cardiovascular (CV) disease risk factors and high CV mortality, with increasing concern over the contribution of antipsychotic medications to cardiometabolic risk. The design of the NIMH-sponsored Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial was driven by a need to understand the efficacy and safety differences between atypical antipsychotics, and between atypical and typical antipsychotics. The CATIE data indicated differences between olanzapine and other antipsychotics in phase 1 on the primary outcome measure, time to drug discontinuation, yet olanzapine was not superior to risperidone in the phase 2 tolerability arm, and was inferior to clozapine in the phase 2 efficacy arm. However, CATIE provided clear confirmation of the metabolic liability for olanzapine and also quetiapine, particularly on measures associated with insulin resistance: fasting triglycerides and central adiposity. Current research is focused on analyzing the adiposity-independent impact of certain antipsychotics on glucose- insulin homeostasis, and the disease-specific biological factors that predispose schizophrenia patients to metabolic dysfunction. The CATIE data also highlighted the high prevalence of metabolic disorders in chronic schizophrenia patients, and the moderating role of gender and race or ethnicity in antipsychotic-associated metabolic adverse effects. In the post-CATIE era, safety concerns remain the primary driver of antipsychotic prescribing habits. Absent compelling efficacy data that differentiates between antipsychotics for nonrefractory schizophrenia, the CATIE results reinforce the need for additional metabolically neutral antipsychotic treatment options, and the importance of ongoing physical health monitoring for schizophrenia patients. © Springer-Verlag Berlin Heidelberg 2010.